Compact multi-color flow cytometer

ABSTRACT

A system, an apparatus, and a method are provided for a modular flow cytometer with a compact size. In one embodiment, the modular flow cytometry system includes the following: a laser system for emitting laser beams; a flow cell assembly positioned to receive the laser beams at an interrogation region of a fluidics stream where fluoresced cells scatter the laser beams into fluorescent light; a fiber assembly positioned to collect the fluorescent light; and a grating system including a dispersive element and a receiver assembly, wherein the dispersive element is positioned to receive the fluorescent light from the fiber assembly and to direct spectrally dispersed light toward the receiver assembly.

CROSS REFERENCE TO RELATED APPLICATION

This patent application is a continuation and claims the benefit of U.S.Provisional patent application Ser. No. 15/498,397 titled COMPACTMULTI-COLOR FLOW CYTOMETER filed on Apr. 26, 2017 by inventors DavidVrane et al., incorporated herein by reference for all intents andpurposes. Application Ser. No. 15/498,397 claims the benefit of U.S.Provisional Patent Application No. 62/327,946 titled COMPACT MULTI-COLORFLOW CYTOMETER filed on Apr. 26, 2016 by inventors David Vrane et al.,incorporated herein by reference for all intents and purposes.

FIELD

The embodiments of the invention relate generally to flow cytometers.

BACKGROUND

A flow cytometer is a biological cell (bio-cell) analysis and countinginstrument. It is used to analyze the physical and chemicalcharacteristics of bio-cells in a fluid as they pass through one or morelaser beams from lasers. The bio-cells are fluorescently labeled andthen excited by the lasers to emit light at correspondent wavelengths.The fluorescence and the scattered light can be detected and measured todetermine various properties of the cells. Up to thousands of cells persecond can be analyzed by a flow cytometer.

Generally, a flow cytometer includes components of fluidics, optics andelectronics. The fluidics system is to line up and transport cells in astream of fluid to the laser beams where they are excited. Any cell ofsubmicron to over 100-μm in size can be analyzed. The optics systemconsists of lasers which excite the cells in the stream and getscattered. Fluorescent labeled cells emit fluorescence, which iscollected by a lens. The laser light scattered by the cells is capturedat forward and side directions. Optical steering mirrors direct thelight signals to the correspondent detectors, such as a photomultipliertube (PMT), an avalanche photodiode (APD) or a PIN diode (diode with awide, undoped intrinsic semiconductor region between a p-typesemiconductor and an n-type semiconductor region). An electronics systemconverts the light signals detected into electronic signals for acomputer to process. Data are collected on each cell. Thecharacteristics of the cells are determined based on their fluorescentand light scattering properties. A large number of cells are analyzed todraw information on the heterogeneity and different subsets within thecell populations. The data are usually presented in the form of singleparameter histograms or as plots of correlated parameters, which arereferred to as cytograms, displaying data in the form of a dot plot, acontour plot, or a density plot.

Flow cytometry has been widely used in the diagnosis of leukemia andhuman immunodeficiency virus (HIV). Flow cytometry is also commonly usedin basic research and clinical trials, such as molecular biology,immunology, and pathology. Flow cytometry has become an important labprocess in transplantation, oncology, hematology, genetics and prenataldiagnosis. Flow cytometry can also be used to help identify cell surfaceprotein variants.

Conventional flow cytometers are large in size due to their complicatedsystem construction. Bench top space is always precious in a lab,especially when many diagnostic instruments compete for presence in thelab and the many tests that must be accommodated to service the variousclients and patients. In a single core lab, there are normally many flowcytometers deployed for service where the size of the flow cytometerbecomes of greater concern.

BRIEF SUMMARY

The embodiments of the invention are summarized by the claims thatfollow below.

BRIEF DESCRIPTIONS OF THE DRAWINGS

FIG. 1 is a perspective view showing the left, front, and top sides of amodular flow cytometry system.

FIG. 2 is a perspective view showing the front, right, and top sides ofthe modular flow cytometry system.

FIG. 3 shows a front-side view of the modular flow cytometry system.

FIG. 4 shows a rear-side view or the modular flow cytometry system.

FIG. 5 shows an optical plate assembly in the top-side of the modularflow cytometry system.

FIG. 6 is a schematic diagram of a detector array signal chain.

DETAILED DESCRIPTION

In the following detailed description of the embodiments of theinvention, numerous specific details are set forth in order to provide athorough understanding. However, it will be obvious to one skilled inthe art that the embodiments of the invention can be practiced withoutthese specific details. In other instances well known methods,procedures, components, and circuits have not been described in detailso as not to unnecessarily obscure aspects of the embodiments of theinvention.

The embodiments of the invention include a method, apparatus and systemfor a modular flow cytometer (modular flow cytometry system) with acompact size.

In conventional systems, there have been efforts on reducing the size ofa flow cytometer. However, so far, the success has been limited to thoseflow cytometers that can handle cells labeled with a limited amount offluorescence colors or dyes (e.g., up to twelve fluorescence colors).Such systems have limited applications in core labs where a flowcytometer is desired to have up to twenty colors in order to accommodatea variety of customer demands; while keeping a common systemconfiguration to increase the operation efficiency; and reduce themanagement and maintenance costs.

Accordingly, a purpose of the invention is to provide a flow cytometerthat is compact in size while having the capability to process cells offluoresces labeled up to fifty (50) colors. A compact flow cytometer isthereby more portable, easier to manage, lower cost to maintain and moreuser friendly in core labs and many hospitals and clinics. Anotherpurpose of the invention to provide an instrument that is more reliableand more energy efficient with lower electromagnetic emission (andthereby lower electromagnetic interference (EMI)) due to the adoption ofmore energy efficient and lower power consuming optoelectronics andelectronics components with better shielding. A reliable instrument isimportant for applications in a medical emergency environment, while alow EMI instrument is critical in a clinical application environment inorder to reduce interferences to other life-saving instrumentation.

The compact size of the modular flow cytometry system is obtained bytaking a system level approach to size reduction. Accordingly, themodular flow cytometry system may also be referred to as a compact flowcytometer or a compact modular flow cytometer. By virtue of modulardesign, advantageous use of subsystem synergies, and innovative use ofcontemporary technology, the modular flow cytometry system achieves asmall package size without compromising performance or serviceability.

FIG. 1 is a perspective view showing the left, front, and top sides of amodular flow cytometry system 100. The modular flow cytometry system 100includes a modular enclosure 199 with an optical plate assembly 110mounted on top of the modular enclosure 199. The system 100 furtherincludes a sample injection tube (SIT) assembly 130, a loader assembly140, an electrical panel assembly 150 including power supplies, and afluidics assembly 120 mounted to or mounted within the modular enclosure199. The system 100 still further includes grating assemblies 160, alaser system 170 having laser emitters, and a flow cell assembly 308.

FIG. 2 is a perspective view showing the front, right, and top sides ofthe modular flow cytometry system 100. The view in FIG. 2 furtherillustrates the SIT assembly 130, the loader assembly 140, and thegrating assemblies 160, including a third grating assembly on a lowershelf/level 299 of the modular enclosure 199. All three gratingassemblies 160 can correspond to all three lasers of the laser system170; alternatively, each of the grating assemblies can correspond to adifferent one of the lasers of the laser system 170. Another embodimentcan include another number (e.g., three or four) of grating assemblies160, depending on the number of lasers in the laser system 170 used ordepending on some other configuration of the cytometry system 100.

FIG. 3 shows a front-side view of the modular flow cytometry system 100.The modular flow cytometry system 100 has dimensions of a width of 520mm, a height of 530 mm, and a depth of about 500 mm without loader or adepth of about 640 mm if including the loader. This size allows atypical lab bench that is 72 inch (1829 mm) long and 24 inch (610 mm)deep to accommodate three modular cytometer systems 100 comfortablyside-by-side on the lab bench.

FIG. 5 shows a top view of the optical plate assembly 110 in the modularflow cytometry system 100. The optical plate assembly 110 includes alaser system 170 having three semiconductor lasers 170A,170B,170C thatdirect excitation into the flow cell assembly 308. The laser system 170attempts to direct the multiple (e.g., three) laser beams in a co-linearmanner toward the flow cell assembly 308. However, the multiple laserbeams can be slightly offset from one another. The laser system 170includes semiconductor lasers 170A,170B,170C having wavelengthstypically at about 405 nanometers (nm), 488 nm, and 640 nm. The outputpower of the 405 nm semiconductor laser is usually greater than 30milliwatts (mW); the output power of the 488 nm semiconductor laser isusually greater than 20 mW; and the output power of the 640 nmsemiconductor laser is usually greater than 20 mW. Controllerelectronics control the semiconductor lasers to operate at a constanttemperature and a constant output power.

An optical system spatially manipulates the optical laser beams570A,570B,570C generated by the semiconductor lasers 170A,170B,170Crespectively. The optical system includes lenses, prisms, and steeringmirrors to focus the optical laser beams through a fluidic window 318(see FIGS. 3 and 5) onto a fluidic stream carrying biological cells (biocells). The focused optical laser beam size is focused for 50-80 microns(μm) across the flow stream and focused for 5-20 μm along the streamflow in the flow cell assembly 308. In FIG. 5, the optical systemincludes beam shapers 530A-530C that receive the laser light from thesemiconductor lasers 170A-170C, respectively. The laser light outputfrom the beam shapers 530A-530C are coupled into mirrors 532A-532Crespectively to direct the laser light 599A,599B,599C towards and intothe flow cell assembly 308 to target particles (e.g. biological cells).The laser light 599A,599B,599C is slightly separated from each other butdirected substantially in parallel by the mirrors 532A-532C into theflow cell assembly 308 through the fluidic window 318.

The laser light beams 599A,599B,599C arrive at the biological cells(particles) in the flow stream in the flow cell assembly 308. The laserlight beams 599A,599B,599C are then scattered by the cells in the flowstream. A forward scatter diode 514 gathers on-axis scattering light. Acollection lens 513 gathers the off-axis scattering light and thefluorescent light and directs them together to a dichromatic mirror 510.The dichromatic mirror 510 focuses the off-axis scattering light onto aside scatter diode 515. The dichromatic mirror 510 focuses thefluorescent light onto at least one fiber head 516. At least one fiberassembly 517 routes the fluorescent light toward at least one gratingassembly 160.

For a more detailed analysis of a biological sample using differentfluorescent dyes and lasers wavelengths, multiple fiber heads 156,multiple fiber assemblies 517, and multiple grating assemblies 160 canbe used. Three fiber heads 516A,516B,516C can be situated in parallel toreceive the fluorescent light and the three fiber assemblies517A,517B,517C can be used to direct the fluorescent light to threegrating assemblies 160A,160B,160C (collectively referred to as gratingassemblies 160) as shown in FIG. 4.

The three fiber heads 516A,516B,516C (and three fiber assemblies517A,517B,517C) are enabled because the three laser light beams599A,599B,599C are slightly offset (e.g., not precisely co-linear).Accordingly, three fiber heads 516A,516B,516C can separately collectlight beam data from fluoresced cells excited by the three laser lightbeams 599A,599B,599C, which have three different wavelengths.Advantageously, the three fiber assemblies 517A,517B,517C can thendirect the collected light into the three gratings (e.g., the grating519 in each of the three grating assemblies 160A,160B,160C) at differentlocations in the modular flow cytometry system 100, such as the top side(e.g., grating assembly 160A mounted to the optical plate 110, gratingassembly 160B mounted to the side plate 112) or a lower bay (e.g.,grating assembly 160C mounted in the lower level/shelf 299) of themodular enclosure 199 as is shown in FIG. 4. The flexibility in locatingthe grating assemblies 160 in the modular flow cytometry system 100 canprovide a more compact footprint and allow the system to be located on abench top or desktop of a bench or desk, respectively.

Alternatively, the modular flow cytometry system 100 can use one grating519 to collect the light beam data. For example, the three fiberassemblies 517A,517B,517C direct light into one grating 519, as opposedto multiple gratings (e.g., the three gratings 519 of the three gratingassemblies 160A,160B,160C). Separation of the light beam data is thenhandled as data processing operations, instead of separating the lightbeam data by using three gratings. Using one grating can be less complexfrom a physical device standpoint. However, with one grating, the dataprocessing operations can be more complex because separation of thelight beam data requires more data manipulation (e.g., identifyingdifferent wavelengths and separating light beam data accordingly).

Cell geometric characteristics can be categorized through analysis ofthe forward scattering data and the side scattering data associated withthe forward scattered light and side scatted light, respectively. Thecells in the fluidic flow are labeled (colored) by dyes of visiblewavelengths ranging from 400 nm to 900 nm. When excited by the lasers,the dyes coloring the cells produce fluorescent light, which arecollected by a fiber assembly 517 and routed toward a grating assembly160. The modular flow cytometry system 100 maintains a relatively smallsize for the optical plate assembly 110 via compact semiconductor lasers170, an 11.5× power collection lens 513, and integrated photomultipliertube (PMT)/avalanche photo-diode (APD) grating assemblies 160 (see FIG.5). The short focal length of the 11.5× power collection lens 513 has anumerical aperture (NA) of about 1.3 facing the fluorescence emissions,and an NA of about 0.12 facing the collection fiber. This significantlyreduces the depth of the instrument. Meanwhile, the grating assembly 160replaces traditional individual PMT filters with compact, on-printedcircuit board (on-PCB) array of detectors (e.g., see detector array 621of the receiver assembly 520 shown in FIG. 6). The compact array ofdetectors in the grating assembly 160 eliminates the need for a spaceconsuming cascade of mirrors and filters in, or at the end of, thecollection path.

Instead, a compact collimating lens 518 at the input of the gratingassembly 160 directs light emitted from the output end of the collectionfiber onto a diffraction grating 519. The diameter of the core of thecollection fiber of the fiber assembly 517 is between about 400 μm and800 μm, and the fiber NA is about 0.12 mm for a core diameter of about600 μm. The fiber output end can be tapered to a core diameter ofbetween about 100 μm and 300 μm for controlling the imaging size ontothe receiving photodiode. The input end of the collection fiber can be alensed fiber to increase the collection NA for allowing use of a fibercore diameter that is less than about 400 μm. Because optical fiber hasthe flexibility to deliver the light anywhere in the system, the use ofoptical fiber as the collection fiber for fluorescence light collectionenables optimization of the location of the receiver assembly 520 andelectronics for a compact flow cytometer 100. The optical performance ofthe grating 519 is designed to have a flat diffraction efficiency over awavelength range of at least 200 nm, preferably more than 400 nm in thevisible wavelength range from 350 nm to 850 nm.

Alternatively, two grating assemblies 160 each with a grating to providetwo gratings 519 in the modular flow cytometry system 100 can be usedalong with a diachronic mirror to separate the wide wavelength rangefluorescence into two spectrum ranges, one spectrum range from 350 nm to600 nm and the other spectrum range from 600 nm to 850 nm. Two gratingsthereby reduce, to half, the requirement on the covered diffractionspectrum range of the gratings. An alternative dispersive element, suchas a linear graded long pass filter, can be used in place of adiffraction grating for the dispersing element 519 for dispersing thefluorescent light.

FIG. 6 is a schematic diagram of at least one detector array signalchain of possibly three or more that are in the modular flow cytometrysystem 100. The light 601 from the collimating lens 518 is coupled intothe grating 519. The grating 519 disperses the light 601 into aspectrally dispersed output light 610. The spectrally dispersed outputlight 610 from the grating 519 is focused directly onto a PCB-mounteddetector array 621. Each detector array 621 is comprised of at least twosets of channels, with each set typically being 8 channels. For example,the detector array 621 in FIG. 6 includes 16 channels formed of two setsof 8 channels. In another embodiment, the PCB-mounted detector array caninclude 8 channels, 9 channels, 10 channels, or some other number ofchannels.

Trans-impedance amplifier circuit 622, one per channel, converts inputcurrent from the detector into an output voltage signal. In eachchannel, the output voltage signal from the trans-impedance amplifiercircuit 622 is coupled into an analog-to-digital converter (ADC) 624.The system 100 enables control of the trans-impedance bias voltage 623into the trans-impedance amplifier circuit 622 of each channel to adjustthe output voltage that is generated. The system 100 then couples eachtrans-impedance bias voltage 623 into each ADC 624.

The ADCs 624 sample the output voltage of the trans-impedance amplifiers622 at a sufficiently high frequency to resolve pulses 625 produced bythe particles (e.g., biological cells) passing through the laserinterrogation region of the fluidics stream. The output pulses from theADCs 624 form a plurality of output waveforms 635 over time. To preservesignal integrity and reduce noise, the system 100 uses electromagneticemission (EMI) shielding 626 on the differential signal wires betweenthe trans-impedance amplifier and ADC of each channel.

Referring again to FIG. 2, the modular flow cytometry system 100includes three grating assemblies 160 each having a detector array. In acase of 8 channels per detector array and three grating assemblies, theflow cytometry system 100 has a total of 24 channels (3 gratingassemblies×8 channels per array). In a case of 16 channels per array andthree grating assemblies, the modular flow cytometry system has a totalof 48-channels (3 grating assemblies×16 channels per array).

Referring again to FIG. 3, the modular flow cytometry system 100includes a modular fluidics assembly 120 of fluidics elements anddevices to control the flow of fluids. The modular fluidics assembly 120can be located in the front of the modular flow cytometry system 100near the flow cell assembly 308. Advantageously, localizing fluidicselements to a single enclosure tends to minimize tube lengths (andassociated chassis accommodations, such as splash shields and tubegalleries) and isolates the fluidics from moisture sensitiveelectronics. Bulkhead connectors 309 for liquid input/output (I/O) portsfor input sheath fluid and output waste fluid are integrated into thefront of the modular fluidics assembly 120, as opposed to the side orback panels of the cytometer system 100. This arrangement saves spaceand improves accessibility to tank lines with the modular flow cytometrysystem 100. The modular fluidics assembly 120 can be removed frommodular flow cytometry system 100 as a module for ease ofserviceability.

During the operation, the fluid system of the modular fluidics assembly120 lines up color labeled cells (also referred to as dyed cells) in afluidic stream, ready to be excited by the one or more laser beams intofluoresced cells. In the modular flow cytometry system 100, one lasercan excite cells of more than 10 individually addressable colors. Forthree lasers in the modular flow cytometry system 100, more than 20individually addressable colors can be excited, detected and analyzed,limited by the available dyes calibrated for applications using flowcytometers. With color detection by dispersive elements instead ofphysical hardware filters, a large number of colors can supported by themodular flow cytometry system 100. With a 3-laser system, the modularflow cytometry system 100 can accommodate more than 14 colors based onthe available flow cytometer dyes on the market.

The sample injection tube (SIT) assembly 130 combines carryoverreduction and z-axis functionalities. This significantly reduces thesize of the loader assembly 140 by allowing loader sample input to usethe sample input location as the manual port 310. The loader assembly140 includes a plate loader 304 as is shown in FIG. 3. To reduce thewidth dimension of the system 100, the plate loader 340 employs an x-θstage motor, as opposed to a more conventional x-y stage motor.

FIG. 4 shows a rear-side view or the modular flow cytometry system 100.The modular flow cytometry system 100 uses a purpose-built, expandable,data acquisition subsystem 411, as shown in FIG. 4. The data acquisitionsubsystem 411 includes a master board 421 and up to five slave boards422 coupled to the master board 421. The master board 421 differs fromthe slave boards 422 in that the master board is populated withadditional components for handling communication functions. In oneembodiment, all boards 421,422 (master and slaves) are equipped witheight 16-bit channels for fluorescence detection, a first 12-bit channelfor forward-scattered light (FSC) detection, and a second 12-bit channelfor side-scattered light (SSC) detection. The data acquisition subsystem411 includes a card cage 420 to receive six boards 421,422 (one masterand five slaves) to provide a 48-channel embodiment of the modular flowcytometry system 100. The card cage 420 has dimensions of about 250 mm(width)×183 mm (height)×117 mm (depth).

A power supply module 412 provides power for the modular flow cytometrysystem 100. In one embodiment, for a 48-channel embodiment, the powersupply module 412 includes three low-noise analog power supplies and onegeneral purpose power supply. The low noise analog power suppliesprovide low noise power to the signal detection electronics (e.g., theADCs 624, photodiode detector array 621 and the trans-impedanceamplifiers 622 of the receiver assembly 520 in the grating assembly 160)isolated from more noisy circuits (e.g., the digital electronics andmotors) in the modular flow cytometry system 100. The general purposepower supply of the power supply module 412 provides power for the dataacquisition, fluidics, SIT, and loader electronics.

CONCLUSION

The embodiments of the invention are thus described. While embodimentsof the invention have been particularly described, they should not beconstrued as limited by such embodiments, but rather construed accordingto the claims that follow below.

While certain exemplary embodiments have been described and shown in theaccompanying drawings, it is to be understood that such embodiments aremerely illustrative of and not restrictive on the broad invention, andthat the embodiments of the invention not be limited to the specificconstructions and arrangements shown and described, since various othermodifications can occur to those ordinarily skilled in the art.

When implemented in software, the elements of the embodiments of theinvention are essentially the code segments to perform the necessarytasks. The program or code segments can be stored in a processorreadable medium or transmitted by a computer data signal embodied in acarrier wave over a transmission medium or communication link. The“processor readable medium” can include any medium that can store ortransfer information. Examples of the processor readable medium includean electronic circuit, a semiconductor memory device, a read only memory(ROM), a flash memory, an erasable programmable read only memory(EPROM), a floppy diskette, a CD-ROM, an optical disk, a hard disk, afiber optic medium, a radio frequency (RF) link, etc. The computer datasignal can include any signal that can propagate over a transmissionmedium such as electronic network channels, optical fibers, air,electromagnetic, RF links, etc. The code segments can be downloaded viacomputer networks such as the Internet, Intranet, etc.

While this specification includes many specifics, these should not beconstrued as limitations on the scope of the disclosure or of what canbe claimed, but rather as descriptions of features specific toparticular implementations of the disclosure. Certain features that aredescribed in this specification in the context of separateimplementations can also be implemented in combination in a singleimplementation. Conversely, various features that are described in thecontext of a single implementation can also be implemented in multipleimplementations, separately or in sub-combination. Moreover, althoughfeatures can be described above as acting in certain combinations andeven initially claimed as such, one or more features from a claimedcombination can in some cases be excised from the combination, and theclaimed combination can be directed to a sub-combination or variationsof a sub-combination. Accordingly, the claimed invention is limited onlyby patented claims that follow below.

1-27. (canceled)
 28. A method of flow cytometry with a flow cytometer,the method comprising: generating a first laser beam of a firstwavelength with a first laser; receiving the first laser beam into aflow cell with fluoresced cells in a fluidics stream wherein thefluoresced cells scatter the first laser beam into fluorescent light;collecting the fluorescent light at one end of a first fiber assembly;receiving the fluorescent light from the opposite end of the first fiberassembly; dispersing the fluorescent light into a spectrally dispersedlight towards a first receiver assembly having a first plurality ofparallel photodiodes in a first photodiode detector array; receiving thespectrally dispersed light with the first photodiode detector array andgenerating a first plurality of current signals respectively with thefirst plurality of parallel photodiodes; receiving the first pluralityof current signals with a first plurality of trans-impedance amplifiercircuits of the first receiver assembly; and generating a firstplurality of output voltage signals with the first plurality oftrans-impedance amplifier circuits.
 29. The method of claim 28, furthercomprising: directing the fluorescent light with the first fiberassembly into a first grating system including the first receiverassembly.
 30. The method of claim 28, wherein the first plurality ofoutput voltage signals represent a first range of different wavelengthsof fluorescent light scattered by the fluoresced cells in the fluidicsstream to analyze cells in the fluidics stream.
 31. The method of claim28, further comprising: sampling the plurality of output voltage signalswith a plurality of analog-to-digital converters and form pulsesassociated with by the fluoresced cells passing through an interrogationregion of the flow cell.
 32. The method of claim 28, further comprising:generating a second laser beam of a second wavelength with a secondlaser; receiving the second laser beam into the flow cell with thefluoresced cells in the fluidics stream wherein the fluoresced cellsscatter the second laser beam into fluorescent light; collecting thefluorescent light at one end of a second fiber assembly; receiving thefluorescent light from the opposite end of the second fiber assembly;dispersing the fluorescent light into a spectrally dispersed lighttowards a second receiver assembly having a second plurality of parallelphotodiodes in a second photodiode detector array; receiving thespectrally dispersed light with the second photodiode detector array andgenerating a second plurality of current signals respectively with thesecond plurality of parallel photodiodes; receiving the second pluralityof current signals with a second plurality of trans-impedance amplifiercircuits of the second receiver assembly; and generating a secondplurality of output voltage signals with the second plurality oftrans-impedance amplifier circuits.
 33. The method of claim 32, whereinthe second plurality of output voltage signals represent a second rangeof different wavelengths of fluorescent light scattered by thefluoresced cells in the fluidics stream to analyze cells in the fluidicsstream.
 34. The method of claim 32, further comprising: generating athird laser beam of a third wavelength with a third laser; receiving thethird laser beam into the flow cell with the fluoresced cells in thefluidics stream wherein the fluoresced cells scatter the third laserbeam into fluorescent light; collecting the fluorescent light at one endof a third fiber assembly; receiving the fluorescent light from theopposite end of the third fiber assembly; dispersing the fluorescentlight into a spectrally dispersed light towards a third receiverassembly having a third plurality of parallel photodiodes in a thirdphotodiode detector array; receiving the spectrally dispersed light withthe third photodiode detector array and generating a third plurality ofcurrent signals respectively with the third plurality of parallelphotodiodes; receiving the third plurality of current signals with athird plurality of trans-impedance amplifier circuits of the thirdreceiver assembly; and generating a third plurality of output voltagesignals with the third plurality of trans-impedance amplifier circuits.35. The method of claim 34, wherein the third plurality of outputvoltage signals represent a third range of different wavelengths offluorescent light scattered by the fluoresced cells in the fluidicsstream to analyze cells in the fluidics stream.
 36. A compact modularflow cytometry system, comprising: a modular enclosure with a compactfootprint configured to rest onto a bench top; an optical plate assemblycoupled to a top of the modular enclosure; a laser system with aplurality of excitation lasers coupled to the optical plate to emit aplurality of laser beams; a flow cell assembly coupled to the opticalplate assembly, the flow cell assembly positioned to receive theplurality of laser beams at an interrogation region of a fluidics streamwhere fluoresced cells scatter the plurality of laser beams intofluorescent light; at least one fiber assembly having at least one fiberhead at one end coupled to the optical plate assembly, the least onefiber head having an input end of at least one collection fiberpositioned to collect the fluorescent light; and at least one gratingsystem coupled to the modular enclosure, the at least one grating systemincluding a dispersive element and a receiver assembly, wherein thedispersive element is positioned to receive the fluorescent light froman output end of the at least one collection fiber and to directspectrally dispersed light toward the receiver assembly.
 37. The compactmodular flow cytometry system of claim 36, wherein: the at least onegrating system is mounted to the optical plate assembly.
 38. The compactmodular flow cytometry system of claim 36, wherein: the at least onegrating system is mounted into a lower shelf of the modular enclosure;and the at least one fiber assembly directs the fluorescent light fromthe optical plate coupled to the top of the modular enclosure towardsthe at least one grating system mounted into the lower shelf of themodular enclosure.
 39. The compact modular flow cytometry system ofclaim 36, wherein: the at least one grating system further includes acollimating lens positioned between the output end of the at least onecollection fiber and the dispersive element.
 40. The compact modularflow cytometry system of claim 36, wherein: the dispersive element ofthe at least one grating system is a diffraction grating to disperse thefluorescent light.
 41. The compact modular flow cytometry system ofclaim 40, wherein the receiver assembly comprises: a photodiode detectorarray positioned to receive the spectrally dispersed light, wherein thephotodiode detector array includes a plurality of channels; andtrans-impedance amplifier circuits configured to convert input currentfrom the photodiode detector array into an output voltage signal foreach channel of the photodiode detector array.
 42. The compact modularflow cytometry system of claim 41, wherein the receiver assembly furthercomprises: analog-to-digital converters coupled to trans-impedanceamplifier circuits, wherein each trans-impedance amplifier circuit iscoupled to a different analog-to-digital converter.
 43. The compactmodular flow cytometry system of claim 36, wherein: the dispersiveelement of the at least one grating system is a linear graded long passfilter to disperse the fluorescent light.
 44. The compact modular flowcytometry system of claim 42, wherein the receiver assembly comprises: aphotodiode detector array positioned to receive the spectrally dispersedlight, wherein the photodiode detector array includes a plurality ofchannels; and trans-impedance amplifier circuits configured to convertinput current from the photodiode detector array into an output voltagesignal for each channel of the photodiode detector array; andanalog-to-digital converters coupled to trans-impedance amplifiercircuits, wherein each trans-impedance amplifier circuit is coupled to adifferent analog-to-digital converter.
 45. (canceled)
 46. The compactmodular flow cytometry system of claim 36, further comprising: a modularfluidics assembly mounted to a front side of the modular enclosure nearthe flow cell assembly, the modular fluidics assembly including a pairof bulkhead connectors for liquid input/output (I/O) ports to coupled totank lines, one bulkhead connector for input sheath fluid, and anotherbulkhead connector for output waste fluid in the front of the modularfluidics assembly.
 47. (canceled)
 48. The compact modular flow cytometrysystem of claim 36, further comprising: an electrical panel assemblymounted to the modular enclosure including a general purpose powersupply isolated from at least one analog power supply supplying power toa photodiode detector array and trans-impedance amplifiers in thereceiver assembly of the least one grating system.
 49. The compactmodular flow cytometry system of claim 36, further comprising: a sampleinjection tube assembly mounted within the modular enclosure, the sampleinjection tube assembly providing z-axis sample loading functionality;and a loader assembly including a plate loader with x-θ stage motor.